Brain Stimulation for the Treatment of Tourette Syndrome

Not Applicable

Completed

Conditions: Tourette Syndrome

Interventions: Device: NeuroPace RNS® System Deep Brain Stimulator

Registration Number: NCT01329198

Lead Sponsor: University of Florida

Brief Summary: The purpose of this trial is to determine whether a particular type of Deep Brain Stimulation (DBS), scheduled Deep Brain stimulation (SBS), is an effective and safe treatment for Tourettte syndrome (TS).

The trial will also examine the brain activity associated with TS and tics and explore the possibility of responsive brain stimulation (RBS).

Detailed Description: DBS is a surgical procedure that seeks to change the brain's electrical signalling by means of applied electrical current. To this end, a wire with tiny stimulating electrodes is implanted into one or both sides of the brain. An electrode is a small piece of metal used to take an electric current to or from a power source. These electrodes are connected under the skin on the scalp to a small electrical unit called an INS (implantable neurostimulator), which is similar to a heart pacemaker. The device sends out electrical impulses that appear to change the normal flow of electricity in the brain.

The wires which house the electrodes will be implanted on both sides of the brain oriented towards the centromedian thalamus-parafascicular complex. This region of the brain has to date the greats number of documented cases revealing significant improvements in motor tics.

This region of the brain will also provide a target where physiological changes related to motor tics are likely to be discovered.

The device we propose for this study has several features that make it more suitable for use in the TS population than other devices. It is self-contained in the skull and brain, and contains no tunneled neck connector wire and no chest pacemaker deice. This will help to lessen infection, and will assist in limiting device-related fractures due to tics involving neck region. Also, the system can record electro-encephalograph data from the area of the electrodes, which will assist us in gathering information about what specific physiological changes are correlated with tics.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 5

Inclusion Criteria

diagnosis of TS must be made by both a neurologist and a psychiatrist and must meet standardized criteria
must have a minimum score on the primary tic rating scale
symptoms must be causing significant impairment in functioning, making it impossible or almost impossible to do daily activities, including work or school and interactions with friends and family, causing severe distress and a poor quality of life
symptoms have not responded well enough to medications prescribed by a neurologist or psychiatrist experienced in treating TS. Must have had trials of drugs from three different classes of drugs that have not worked.
must have received stable and effective treatment of any other existing medical or psychological problems for the past 6 months.
current TS related-medication(s) must be stable for at least a month without a dose change prior to surgery and must be willing to keep these medications stable and unchanged throughout the study or must be off of TS-related medications for at least three months prior to surgery
If tics involve only one group of muscles or might be controllable by botulinum toxin treatment, must try botulinum treatment before considering surgery.
must have a negative urine drug screen
must give informed consent

Exclusion Criteria

have a simple motor tic or movement disorder other than TS, or medication-related movement disorders from TS medications
have had any previous brain surgery including deep brain stimulation, ablative capsulotomy or cingulotomy
have another psychiatric condition (including body dysmorphic disorder, a delusional disorder or a biological brain disorder), dementia or cognitive dysfunction that would place subject at risk for worsening cognition and/or may impact ability to comply with study procedures. Also included is any other psychiatric disorder that requires medications or treatments that would interfere with the functioning of the DBS device.
have any significant substance abuse or dependence (e.g., stimulants, alcohol, opiates, benzodiazepines) within the past six months
have a severe medical disease including cardiovascular disorder, lung disorder, kidney disease, chronic neurological disease, hematological disease, or frailty that impacts tolerability of the surgery as judged by the screening physicians
pre-surgery MRI is considered abnormal. You may also be excluded if your brain is considered very small.
have a history of serious suicidal behavior, are unable to control suicide attempts, or are currently at risk of suicide, in the judgement of the investigator
have head-banging tics or tics that have the potential to damage the RNS System
are currently pregnant or breast-feeding, plan to become pregnant during the study, or are not using effective contraception
are currently enrolled in another investigational study
have an implant such as a pacemaker or neurostimulator containing electrical circuitry or that generates electrical signals
have any metal orthopedic pins or plates, metal orthodontics, or non-removable body jewelry
require diathermy treatments during physical or occupational therapy
have a problem that will require repeat Magnetic Resonance Imaging (MRI) scans

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Delayed Activation - Deep Brain Stimulation (DBS)	NeuroPace RNS® System Deep Brain Stimulator	Delayed Activation stimulation in which no electrical charge is delivered through the Neuropace RNS (responsive neurostimulation) system for the first 59 days. On Day 60, all subjects will be programmed to receive active stimulation. * There will be a one month post-operative period during which stimulation is not turned on. * One month post-implant, subjects will be randomized one to one in a blinded fashion to receive active or sham stimulation. * By Day 60, all subjects will be programmed to receive active stimulation. Physiological data will be collected for Specific Aim 2 of the study. * Both the sham and the active groups (3 subjects in each group) will undergo identical programming procedures at 30 and 60 days.
Immediate Activation - Deep Brain Stimulation (DBS)	NeuroPace RNS® System Deep Brain Stimulator	Active stimulation through the Neuropace RNS (responsive neurostimulation) system at settings to maximally reduce tic frequency \& severity, while limiting potential stimulation-induced side-effects. * There will be a one month post-operative period during which stimulation is not turned on. * One month post-implant, subjects will be randomized one to one in a blinded fashion to receive active or sham stimulation. * By Day 60, all subjects will be programmed to receive active stimulation. Physiological data will be collected for Specific Aim 2 of the study. * Both the sham and the active groups (3 subjects in each group) will undergo identical programming procedures at 30 and 60 days.

Primary Outcome Measures

Name	Time	Method
Mean Change in Yale Global Tic Severity Scale (YGTSS) Scores From Baseline to 6 Months Across All Study Participants Presented	Baseline to 6 Months	The Yale Global Tic Severity Scale (YGTSS) is a semistructured clinician-rated instrument that assesses the severity and frequency of motor and phonic tics over the previous week. Five index scores are obtained during the assessment, where higher scores indicate greater frequency or severity. These indices are: * Total Motor Tic Score (0-25) * Total Phonic Tic Score (0-25 * Total Tic Score (0-50) * Overall Impairment Rating (0-50) * Global Severity Score (0-7) The YGTSS Total Score is obtained by adding the Total Tic Score to the Overall Impairment Rating. The efficacy of the intervention will be assessed by comparing each subject's 6-month YGTSS Total Score to the pre-operative value for the same patient. Efficacy is considered 50% or greater reduction in this score.

Secondary Outcome Measures

Name	Time	Method
Correlation of Tics and Neural Physiology	Baseline to 6 Months	Electrical recordings of electroencephalography activity were taken from each subject's implanted leads at each visit from baseline to 6 months. At baseline, the recordings were taken with the device in the off state (not stimulating), while at the 6 month visits the recordings were taken with the subject's device set to optimal parameters for tic control. Using Pearson's correlation coefficient, the variations in frequency and power which were observed were correlated with the Yale Global Tic Severity (YGTSS) scores obtained during primary outcome testing.